PROJECT SUMMARY Alcohol use and risk for alcohol-related harm is prevalent in adolescence and young adulthood (i.e., age 12- 25), and this is also a critical time in human brain development. In response to RFA-AA-17-004, this application proposes the Administrative Resource (AR) of the National Consortium on Alcohol and Neurodevelopment in Adolescence second phase (NCANDA-2), located at UC San Diego. The overarching consortium goals are to determine the predictors and effects of heavy alcohol use in adolescence and young adulthood in a demographically representative sample of adolescents. This consortium was designed to synergize the diverse scientific expertise and research experience of the investigators at each site. This consortium reflects seven applications: NCANDA - Administrative Resource (UCSD) and NCANDA - Data Analysis Resource (SRI), and five cross-national Research Project Sites, located at Duke University (Duke), Oregon Health Science University (OHSU), University of Pittsburgh (Pitt), SRI International (SRI), and UC San Diego (UCSD). Recruited at ages 12 through 21 across the five sites, a high-risk enhanced community sample of 831 subjects completed a baseline assessment and three annual follow-up assessments in an accelerated longitudinal design. NCANDA-2 will continue to follow this cohort through the typical age of lifetime peak drinking, using multimodal neuroimaging, cognitive testing, behavioral interviews, biospecimen collection, and technology- enhanced assessment in the natural environment. Examination of alcohol consequences will focus on structural and functional maturation of brain areas that actively develop during adolescence, are involved in self-regulation and reward response, and appear vulnerable to neurotoxic effects of alcohol. Five aims specified in the RFA will be systematically tested with a focus on adolescent substance use and neuromaturational trajectories. Each Research Project Site collaborates with another site on 1-2 additional aims. UCSD, OHSU, and Duke are examining brain recovery in heavy drinkers over 4 weeks of monitored abstinence. Pitt and SRI collaborate to study relations between heavy drinking, sleep characteristics, and brain development. We are examining the influence of heavy drinking on inhibitory dysfunction and the extent to which this mediates cognitive performance, using longitudinal fMRI connectivity analysis during anti-saccade (Pitt, Duke) and Stroop match-to-sample (SRI and UCSD) tasks. With the additional development-specific longitudinal data provided by this renewal, we will determine the effects of alcohol exposure on the developmental trajectory of the adolescent human brain, and identify preexisting psychobiological vulnerabilities that may put an adolescent or young adult at elevated risk for an alcohol use disorder or other adverse life outcome.